Research Progress in the Role of Testosterone in Male Depression

Jiamin FU, Qi GUO, Xiaoyu CHEN

Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (2) : 274-280.

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Abbreviation (ISO4): Acta Academiae Medicinae Sinicae      Editor in chief: Xuetao CAO

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Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (2) : 274-280. DOI: 10.3881/j.issn.1000-503X.16142
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Research Progress in the Role of Testosterone in Male Depression

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Abstract

As the social pressure is increasing,the incidence of depression is growing.Testosterone is synthesized and secreted through the hypothalamic-pituitary-gonadal axis,which plays a regulatory role in men’s mental health.Studies have shown that low testosterone levels,clinical hypogonadism,and androgen deprivation therapy-induced testosterone deficiency are significantly associated with male depression,while there are still many uncertainties about the mechanism of their effects.Given that low testosterone levels may serve as a characteristic biomarker of male depression risk,testosterone replacement therapy may have a good therapeutic effect on male depression.This article focuses on assessing the role of testosterone levels and related clinical therapies in mood regulation in men.

Key words

testosterone / depression / testosterone replacement therapy / hypogonadism / androgen deprivation therapy

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Jiamin FU , Qi GUO , Xiaoyu CHEN. Research Progress in the Role of Testosterone in Male Depression[J]. Acta Academiae Medicinae Sinicae. 2025, 47(2): 274-280 https://doi.org/10.3881/j.issn.1000-503X.16142

References

[1]
Patel V, Chisholm D, Parikh R, et al. Addressing the burden of mental,neurological,and substance use disorders:key messages from disease control priorities,3rd edition[J]. Lancet, 2016, 387(10028):1672-1685.DOI:10.1016/s0140-6736(15)00390-6.
[2]
Otte C, Gold SM, Penninx BW, et al. Major depressive disorder[J]. Nat Rev Dis Primers, 2016,2:16065.DOI:10.1038/nrdp.2016.65.
[3]
Shores MM, Sloan KL, Matsumoto AM, et al. Increased incidence of diagnosed depressive illness in hypogonadal older men[J]. Arch Gen Psychiatry, 2004, 61(2):162-167.DOI:10.1001/archpsyc.61.2.162.
[4]
Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism:an endocrine society clinical practice guideline[J]. J Clin Endocrinol Metab, 2018, 103(5):1715-1744.DOI:10.1210/jc.2018-00229.
[5]
Zitzmann M. Testosterone,mood,behaviour and quality of life[J]. Andrology, 2020, 8(6):1598-1605.DOI:10.1111/andr.12867.
[6]
Yeap BB. Hormonal changes and their impact on cognition and mental health of ageing men[J]. Maturitas, 2014, 79(2):227-235.DOI:10.1016/j.maturitas.2014.05.015.
[7]
Barrett-Connor E, Von Mühlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men:the rancho bernardo study[J]. J Clin Endocrinol Metab, 1999, 84(2):573-577.DOI:10.1210/jcem.84.2.5495.
[8]
Fischer S, Ehlert U, Amiel Castro R. Hormones of the hypothalamic-pituitary-gonadal(HPG)axis in male depressive disorders-a systematic review and meta-analysis[J]. Front Neuroendocrinol, 2019,55:100792.DOI:10.1016/j.yfrne.2019.100792.
[9]
Lunenfeld B, Mskhalaya G, Zitzmann M, et al. Recommendations on the diagnosis,treatment and monitoring of testosterone deficiency in men[J]. Aging Male, 2021, 24(1):119-138.DOI:10.1080/13685538.2021.1962840.
[10]
Khripun I, Vorobyev S, Belousov I, et al. Influence of testosterone substitution on glycemic control and endothelial markers in men with newly diagnosed functional hypogonadism and type 2 diabetes mellitus:a randomized controlled trial[J]. Aging Male, 2019, 22(4):241-249.DOI:10.1080/13685538.2018.1506918.
[11]
Indirli R, Lanzi V, Arosio M, et al. The association of hypogonadism with depression and its treatments[J]. Front Endocrinol(Lausanne), 2023,14:1198437.DOI:10.3389/fendo.2023.1198437.
[12]
Lašaitė L, Čeponis J, Preikša RT, et al. Effects of two-year testosterone replacement therapy on cognition,emotions and quality of life in young and middle-aged hypogonadal men[J]. Andrologia, 2017, 49(3).DOI:10.1111/and.12633.
[13]
Westley CJ, Amdur RL, Irwig MS. High rates of depression and depressive symptoms among men referred for borderline testosterone levels[J]. J Sex Med, 2015, 12(8):1753-1760.DOI:10.1111/jsm.12937.
[14]
Almeida OP, Yeap BB, Hankey GJ, et al. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men[J]. Arch Gen Psychiatry, 2008, 65(3):283-289.DOI:10.1001/archgenpsychiatry.2007.33.
[15]
Gonçalves WS, Gherman BR, Abdo CHN, et al. Prevalence of sexual dysfunction in depressive and persistent depressive disorders:a systematic review and meta-analysis[J]. Int J Impot Res, 2023, 35(4):340-349.DOI:10.1038/s41443-022-00539-7.
[16]
Rothmore J. Antidepressant-induced sexual dysfunction[J]. Med J Aust, 2020, 212(7):329-334.DOI:10.5694/mja2.50522.
[17]
Melloni C, Nelson A. Effect of androgen deprivation therapy on metabolic complications and cardiovascular risk[J]. J Cardiovasc Transl Res, 2020, 13(3):451-462.DOI:10.1007/s12265-019-09942-w.
[18]
Siebert AL, Lapping-Carr L, Morgans AK. Neuropsychiatric impact of androgen deprivation therapy in patients with prostate cancer:current evidence and recommendations for the clinician[J]. Eur Urol Focus, 2020, 6(6):1170-1179.DOI:10.1016/j.euf.2020.05.014.
[19]
Russell N, Grossmann M. Management of bone and metabolic effects of androgen deprivation therapy[J]. Urol Oncol, 2021, 39(10):704-712.DOI:10.1016/j.urolonc.2018.10.007.
[20]
Izard JP, Siemens DR. Androgen deprivation therapy and mental health:impact on depression and cognition[J]. Eur Urol Focus, 2020, 6(6):1162-1164.DOI:10.1016/j.euf.2019.11.010.
[21]
Alwhaibi A, Alsanea S, Almadi B, et al. Androgen deprivation therapy and depression in the prostate cancer patients:review of risk and pharmacological management[J]. Aging Male, 2022, 25(1):101-124.DOI:10.1080/13685538.2022.2053954.
[22]
Pirl WF, Siegel GI, Goode MJ, et al. Depression in men receiving androgen deprivation therapy for prostate cancer:a pilot study[J]. Psychooncology, 2002, 11(6):518-523.DOI:10.1002/pon.592.
[23]
Chung SD, Kao LT, Lin HC, et al. Patients receiving androgen deprivation therapy for prostate cancer have an increased risk of depressive disorder[J]. PLoS One, 2017, 12(3):e0173266.DOI:10.1371/journal.pone.0173266.
[24]
Dinh KT, Reznor G, Muralidhar V, et al. Association of androgen deprivation therapy with depression in localized prostate cancer[J]. J Clin Oncol, 2016, 34(16):1905-1912.DOI:10.1200/jco.2015.64.1969.
[25]
Parhar IS, Ogawa S, Ubuka T. Reproductive neuroendocrine pathways of social behavior[J]. Front Endocrinol(Lausanne), 2016,7:28.DOI:10.3389/fendo.2016.00028.
[26]
Höfer P, Lanzenberger R, Kasper S. Testosterone in the brain:neuroimaging findings and the potential role for neuropsychopharmacology[J]. Eur Neuropsychopharmacol, 2013, 23(2):79-88.DOI:10.1016/j.euroneuro.2012.04.013.
[27]
Hajszan T, MacLusky NJ, Leranth C. Role of androgens and the androgen receptor in remodeling of spine synapses in limbic brain areas[J]. Horm Behav, 2008, 53(5):638-646.DOI:10.1016/j.yhbeh.2007.12.007.
[28]
Bramen JE, Hranilovich JA, Dahl RE, et al. Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity[J]. Cereb Cortex, 2011, 21(3):636-646.DOI:10.1093/cercor/bhq137.
[29]
尹一淑, 刘军莲, 王佳平, 等. 抑郁症相关发病机制研究进展[J]. 医学综述, 2022, 28(12):2368-2372.
[30]
McQueen JK, Wilson H, Sumner BE, et al. Serotonin transporter(SERT)mRNA and binding site densities in male rat brain affected by sex steroids[J]. Brain Res Mol Brain Res, 1999, 63(2):241-247.DOI:10.1016/s0169-328x(98)00281-2.
[31]
Tanaka M, Csabafi K, Telegdy G. Neurotransmissions of antidepressant-like effects of kisspeptin-13[J]. Regul Pept, 2013, 180:1-4.DOI:10.1016/j.regpep.2012.08.017.
[32]
Viau V. Functional cross-talk between the hypothalamic-pituitary-gonadal and-adrenal axes[J]. J Neuroendocrinol, 2002, 14(6):506-513.DOI:10.1046/j.1365-2826.2002.00798.x.
[33]
Oyola MG, Handa RJ. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes:sex differences in regulation of stress responsivity[J]. Stress, 2017, 20(5):476-494.DOI:10.1080/10253890.2017.1369523.
[34]
Williamson M, Bingham B, Gray M, et al. The medial preoptic nucleus integrates the central influences of testosterone on the paraventricular nucleus of the hypothalamus and its extended circuitries[J]. J Neurosci, 2010, 30(35):11762-11770.DOI:10.1523/jneurosci.2852-10.2010.
[35]
Frye CA, Edinger K, Sumida K. Androgen administration to aged male mice increases anti-anxiety behavior and enhances cognitive performance[J]. Neuropsychopharmacology, 2008, 33(5):1049-1061.DOI:10.1038/sj.npp.1301498.
[36]
Song RX, McPherson RA, Adam L, et al. Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation[J]. Mol Endocrinol, 2002, 16(1):116-127.DOI:10.1210/mend.16.1.0748.
[37]
Wang C, Swerdloff RS. Testosterone replacement therapy in hypogonadal men[J]. Endocrinol Metab Clin North Am, 2022, 51(1):77-98.DOI:10.1016/j.ecl.2021.11.005.
[38]
Yabluchanskiy A, Tsitouras PD. Is testosterone replacement therapy in older men effective and safe[J]. Drugs Aging, 2019, 36(11):981-989.DOI:10.1007/s40266-019-00716-2.
[39]
Snyder PJ, Bhasin S, Cunningham GR, et al. Lessons from the testosterone trials[J]. Endocr Rev, 2018, 39(3):369-386.DOI:10.1210/er.2017-00234.
[40]
Amiaz R, Seidman SN. Testosterone and depression in men[J]. Curr Opin Endocrinol Diabetes Obes, 2008, 15(3):278-283.DOI:10.1097/MED.0b013e3282fc27eb.
[41]
Zarrouf FA, Artz S, Griffith J, et al. Testosterone and depression:systematic review and meta-analysis[J]. J Psychiatr Pract, 2009, 15(4):289-305.DOI:10.1097/01.pra.0000358315.88931.fc.
[42]
Amanatkar HR, Chibnall JT, Seo BW, et al. Impact of exogenous testosterone on mood:a systematic review and meta-analysis of randomized placebo-controlled trials[J]. Ann Clin Psychiatry, 2014, 26(1):19-32.
[43]
Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men:a systematic review and meta-analysis[J]. JAMA Psychiatry, 2019, 76(1):31-40.DOI:10.1001/jamapsychiatry.2018.2734.
[44]
Walther A, Ehlert U, Schneeberger M, et al. Evaluation of a male-specific psychotherapeutic program for major depressive disorder compared to cognitive behavioral therapy and waitlist:study protocol for a six-arm randomized clinical superiority trial examining depressed eugonadal and hypogonadal men receiving testosterone[J]. Front Psychiatry, 2023,14:1129386.DOI:10.3389/fpsyt.2023.1129386.
[45]
Vartolomei MD, Kimura S, Vartolomei L, et al. Systematic review of the impact of testosterone replacement therapy on depression in patients with late-onset testosterone deficiency[J]. Eur Urol Focus, 2020, 6(1):170-177.DOI:10.1016/j.euf.2018.07.006.
[46]
陈美惠, 贾佳, 曹燕丽, 等. 抑郁症患者性激素异常及治疗的研究进展[J]. 东南国防医药, 2021, 23(6):633-636.
[47]
Handelsman DJ, Wittert GA. Testosterone and depression symptoms in aging men[J]. J Clin Endocrinol Metab, 2024, 109(9):e1798-e1799.DOI:10.1210/clinem/dgae093.
[48]
Bhasin S, Seidman S, Travison TG, et al. Depressive syndromes in men with hypogonadism in the TRAVERSE Trial:response to testosterone-replacement therapy[J]. J Clin Endocrinol Metab, 2024, 109(7):1814-1826.DOI:10.1210/clinem/dgae026.
[49]
Amore M, Scarlatti F, Quarta AL, et al. Partial androgen deficiency,depression and testosterone treatment in aging men[J]. Aging Clin Exp Res, 2009, 21(1):1-8.DOI:10.1007/bf03324891.
[50]
Niu L, Du Z, Xie Z, et al. Total testosterone plays a crucial role in the pathway from hypothyroidism to broad depression in women[J]. J Affect Disord, 2024, 359:164-170.DOI:10.1016/j.jad.2024.05.085.
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